This proposal requests partial support for the Gordon Research Conference (GRC) series on Autophagy (3 conferences) to be held in Il Ciocco, Italy April 25-30, 2010, and in 2012 and 2014 at yet to be determined sites. Autophagy is a fundamental cellular homeostatic mechanism affecting normal aging and a wide spectrum of major human disease categories. These diseases are significant as standalone entities while being associated with aging: cancer, neurodegeneration, inflammation, muscle and immune diseases, and metabolic disorders. The broad and long term goal of this GRC series is to promote an integrated approach in defining the rapidly expanding role of autophagy in physiological and pathological processes that underlie human aging and diseases. The Autophagy GRC series will facilitate elucidation of the autophagy pathway and how autophagy pertains to normal cell survival and death pathways or their anomalies. The specific aims of these meetings will be to convene 40 speakers and discussion leaders that represent critical areas of autophagy research with a total of over 120 participants for three (2010, 2012, and 2014) five day conferences. The program in 2010 will feature a keynote address and eight sessions that broadly address current issues in regulation of autophagy, autophagy signaling, autophagy machinery, origin of the autophagosome, selective autophagy, and roles of autophagy in metabolic diseases and cancer, innate and adaptive immunity, aging and neurology. In addition, two evening poster sessions will permit all participants to contribute to these topics. In 2012 and 2014, similar programs will cover fundamental aspects of autophagy and place continued and increased emphasis on its role in aging, neurodegeneration, myopathies, metabolic disease, cancer, and immunology including infection, inflammation and autoimmunity. The significance of this application is that the Autophagy GRCs have become the centerpiece of the yearly series of conferences that critically influence, direct and propel research in the international community of autophagy scholars. These conferences bring together investigators who are at the forefront of the autophagy field, and provide opportunities for junior scientists and graduate students to present their work in poster format and exchange ideas with leaders in the field thus nurturing the next generation of autophagy research leaders. The health relatedness of this application is that autophagy directly impacts a wide spectrum of human health and disease states including aging, neurodegeneration, cancer, metabolic disorders, myodegeneration, immune functions and inflammatory diseases. The research spurred by GRC meetings on autophagy will lead to a greater understanding of normal aging processes;help to develop new approaches in treatments of neurodegeneration, muscle atrophy, cancer, metabolic diseases, infection, chronic inflammation and immune disorders. PUBLIC HEALTH RELEVANCE: Autophagy is a newly appreciated fundamental biological process that impacts nearly all facets of human health, including aging, neurodegeneration, cancer, infection and immunity, inflammation and allergy, metabolic diseases and diabetes, muscle atrophy, etc. The growing realization of the broad impact of autophagy on human health is in part the result of vigorous scientific exchange facilitated by previous Gordon Research Conferences (GRC) on Autophagy. The Autophagy GRCs have been instrumental in the discovery of previously unknown connections between autophagy and human health and the translation of presently acquired knowledge into new drugs and novel treatments. In sum, the Autophagy GRCs represent a key venue fueling the unprecedented 360o growth of this field within what has emerged as an autophagy-based continuum of seemingly diverse human diseases, offering development of previously unanticipated but realistic treatments for a broad spectrum of disorders. Many of the leaders in this field are practicing physicians, further attesting to the direct relationship of autophagy to human health, aging, and disease states.